EP
The disclosure provides EP 2 receptor agonist compounds and methods for using the compounds for treating conditions which can be alleviated by agonism of an EP 2 receptor.
1. A compound of formula (I):
or a salt thereof, wherein:
R 5 is an optionally substituted phenyl group where the substituents are selected from the group consisting of: unsubstituted C 1-4 alkyl, C 1-4 alkoxy, —CF 3 , halo, acyl, amino, and alkoxylene;
where Q is CH;
R 3 is selected from the group consisting of H, F, Cl, optionally substituted C 1-4 alkyl, C 1-4 alkoxy, C 5-7 aryl and C 5-7 aryl-C 1-4 alkyl groups;
R 4 is selected from the group consisting of H, F, Cl, optionally substituted C 1-4 alkyl, C 1-4 alkoxy, C 5-7 aryl, and C 5-7 aryl-C 1-4 alkyl groups;
R 6 is selected from the group consisting of H, F, Cl, optionally substituted C 1-4 alkyl, C 1-4 alkoxy, C 5-7 aryl, and C 5-7 aryl-C 1-4 alkyl groups;
D is selected from the group consisting of
B is selected from the group consisting of
where one of R P3 and R P4 is —C m alkylene-R 2 and the other of R P3 and R P4 is H, m and n are independently 0 or 1, and m+n=1 or 2; and additionally when R P3 is —C m alkylene-R 2 , m is 2 or 3, and m+n=2, 3 or 4, and when R 2 is tetrazol-5-yl, m+n is 0; or
where one of R P3 and R P4 is —O—CH 2 —R 2 , and the other of R P3 and R P4 is H, n is 0;
R N is H or optionally substituted C 1-4 alkyl;
R 2 is either:
(i) —CO 2 H (carboxy);
(ii) —CONH 2 ;
(iii) —CH 2 —OH (methoxy); or
(iv) tetrazol-5-yl.
2. A compound according to claim 1 , wherein R 5 is unsubstituted phenyl.
3. A compound according to claim 1 , wherein:
(i) R 3 , R 4 and R 6 are H; or
(ii) one of R 3 , R 4 and R 6 is Cl or F.
4. A compound according to claim 1 , wherein R N is H.
5. A compound according to claim 1 , wherein B is:
6. A compound according to claim 1 , wherein R 2 is —CO 2 H or tetrazoly-5-yl.
7. A compound according to claim 6 , wherein R 2 is —CO 2 H.
8. A compound according to claim 1 , wherein R P4 is H, and R P3 is —CH═CH—R 2 .
9. A compound according to claim 1 , wherein R P3 is —O—CH 2 —R 2 .
10. A compound which is:
{3-[(4-Chloro-biphenyl-3-carbonyl)-amino]-phenyl}-acetic acid;
{3-[(6-Fluoro-biphenyl-3-carbonyl)-amino]-phenyl}-acetic acid;
{3-[(Biphenyl-3-carbonyl)-amino]-phenyl}-acetic acid;
{3-[(4-Fluoro-biphenyl-3-carbonyl)-amino]-phenyl}-acetic acid;
{3-[(5-Fluoro-biphenyl-3-carbonyl)-amino]-phenyl}-acetic acid;
3-{3-[(4-Fluoro-biphenyl-3-carbonyl)-amino]-phenyl}-acrylic acid;
3-{3-[(4,3′-Difluoro-biphenyl-3-carbonyl)-amino]-phenyl}-acrylic acid;
{3-[(4,3′-Difluoro-biphenyl -3-carbonyl )-amino]-phenyl}-acetic acid;
3-{3- [(4,4′-Difluoro-biphenyl-3-carbonyl)-amino]-phenyl }acrylic acid;
[3-(Biphenyl-3-ylcarbamoyl)-phenyl]-acetic acid;
{3-[(3′-Chloro-4-fluoro-biphenyl-3-carbonyl)-amino]-phenoxy}-acetic acid;
3-{3-[(3′-Chloro-4-fluoro-biphenyl-3 -carbonyl)-amino]-phenyl}-acrylic acid;
{3-[(3′,5′-Dichloro-4-fluoro-biphenyl-3-carbonyl) -amino]-phenoxy}-acetic acid;
3-{3 -[(3′, 5′-Dichloro-4-fluoro-biphenyl-3-carbonyl)-amino]-phenyl}-acrylic acid;
{3-[(4-Fluoro-biphenyl-3-carbonyl)-amino]-phenoxy}-acetic acid;
{3-[(4,3′-Difluoro-biphenyl-3-carbonyl)-amino]-phenoxy}-acetic acid;
{3-[(4,4′-Difluoro-biphenyl-3-carbonyl)-amino]-phenoxy}-acetic acid; or
4-Fluoro-biphenyl-3-carboxylic acid {3-[2-(lH-tetrazol-5yl)-vinyl]phenyl}-amide.
11. The compound of claim 10 wherein the compound is:
3-{3-[(4-Fluoro-biphenyl-3-carbonyl)-amino]-phenyl}-acrylic acid;
3-{3-[(4,3′-Difluoro-biphenyl-3-carbonyl)-amino]-phenyl}-acrylic acid;
3-{3-[(4,4′-Difluoro-biphenyl-3-carbonyl)-amino]-phenyl}-acrylic acid;
{3-[(4,4′-Difluoro-biphenyl-3-carbonyl)-amino]-phenoxy}-acetic acid; or
{3-[(4,3′-Difluoro-biphenyl-3-carbonyl)-amino]-phenoxy}-acetic acid.
12. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.
13. A method of treating a condition which can be alleviated by agonism of an EP 2 receptor, which method comprises administering to a patient, in need of treatment, an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the condition is glaucoma or ocular hypertension.